Willingness to Pay for Sensory Attributes of Intranasal Corticosteroids Among Patients With Allergic Rhinitis

OBJECTIVES: Sensory attributes of intranasal corticosteroids (INSs) differ by product based on chemical composition. We previously reported that patients are able to demonstrate preferences for certain INS sensory attributes, which may affect their willingness to adhere to therapy. As part of the same study, we also sought to determine if these same patients are willing to pay for products not containing certain sensory attributes. METHODS: We conducted a 2-part cross-sectional study of 120 patients with allergic rhinitis at 4 allergy and immunology clinics in the United States in November and December 2003. In the first part of the study, the patients chose between pairs of hypothetical INS products that differed in the intensity of 6 sensory attributes (smell, taste, aftertaste, throat rundown, nose runout, and feel of spray in nose/throat; results were reported in the Annals of Allergy, Asthma and Immunology [2004;93:345-50]). In the second part of the study, reported here, discrete choice experiment methodology was used in which the patients chose among hypothetical INS products that differed in the intensity of the 6 sensory attributes and monthly copayments of $15, $30, and $50. Each sensory attribute was characterized by 3 intensity levels, e.g., no aftertaste (mild intensity), weak aftertaste (moderate intensity), or strong aftertaste (severe intensity). The strength of preferences, shown as marginal willingness to pay to avoid certain sensory attributes, was measured in U.S. dollars per month. We also evaluated the effect of annual household income on willingness to pay. RESULTS: Demographic results indicated that 86.7% of participants had prior experience with at least 2 INS products. Seven patients (5.8%) were excluded from the willingness-to-pay analysis due to inconsistent responses to the logic checks used to confirm patient engagement in the study instrument. On average, the 113 remaining patients were willing to pay $11 (95% confidence interval [CI], $9-$13) per month in 2003 dollars to get an INS with no smell instead of strong smell, $12 (95% CI, $10-$14) for no taste instead of strong taste, $20 (95% CI, $18-$22) for no aftertaste instead of strong aftertaste, $10 (95% CI, $9-$12) for no throat rundown instead of a lot of throat rundown, $11 (95% CI, $9-$13) for no nose runout instead of a lot of nose runout, and $6 (95% CI, $4-$8) for a spray with a wet feel instead of a dry feel. Comparing moderate intensity levels of each sensory attribute with the mildest, only 3 attributes had statistically significant willingness to pay: aftertaste, throat rundown, and nose runout. Patients with a higher income were willing to pay more to avoid a lot of throat rundown and nose runout than those with a low income (P less than0.01), but this relationship did not hold for the other sensory attributes. CONCLUSIONS: Patients demonstrated significant willingness to pay to avoid certain sensory attributes of INSs. Sensory attributes of INS products appear to be potentially important considerations when evaluating alternative INS products for drug therapy selection or formulary placement.

and amount of spray running out of nose or running down throat. Attributes were assessed using the Sensory Perceptions Questionnaire, 10 which has 23 items, 7 of which solicit patient preferences. In analyses that included all responding patients, 54.4% of patients in the first study preferred budesonide and 37.8% preferred fluticasone (P <0.022). In the second study, 47.4% preferred budesonide and 41.1% preferred fluticasone (difference was not significant).
In a randomized, double-blind, crossover trial, Bachert and El-Akkad 7 reported that patients preferred the odor of triamcinolone acetonide aqueous nasal spray and judged it to be less strong compared with fluticasone propionate or mometasone furoate nasal sprays, and the taste of triamcinolone acetonide aqueous nasal spray was preferred to mometasone furoate. Patient preferences were rated on a 14-item nasal spray evaluation questionnaire, which evaluates the acceptability of the drug and associated sensory perceptions immediately (10 items) and 2 minutes after (4 items) drug administration, using a 100-point rating scale. Both Bachert and El-Akkad 7 and Shah et al. 9 assessed patients' perceptions of and preferences for certain INS sensory attributes, but they did not assess the strength of patient preferences in terms of their willingness to pay for an INS with the sensory attributes they prefer or would like to avoid.
Reissman et al. 11 conducted a cost-efficiency study to determine the relative prescribed dosages of 4 INSs and compare economic differences resulting from these prescribing behaviors.
In their study, using data from the IMS National Disease and Therapeutic Index for calendar year 2002, Reissman et al. found differences in the average number of sprays prescribed daily and, therefore, differences in the average cost per prescribed day of therapy among budesonide, fluticasone, mometasone, and triamcinolone nasal sprays.
Keith et al. 12 conducted a cost-benefit study with patients receiving either intranasal budesonide by Turbuhaler or aqueous spray. In this study, patients completed a willingness-to-pay questionnaire to measure treatment benefits; however, adaptive preferences were not assessed. Costs were then compared with the willingness-to-pay data as part of the treatment benefit analysis. Results of this study indicated there was no difference in cost, willingness to pay, or cost-benefit when comparing delivery modes. Additionally, it was suggested that willingnessto-pay questionnaires may be a useful method to assess a therapy' s benefit. These previous cost studies, however, did not incorporate patient preferences for INS sensory attributes.
The aim of the current study was to integrate 2 important concepts: patient preferences for INS sensory attributes and treatment cost. We assessed allergic rhinitis patients' preferences for various sensory attributes and willingness to pay for products with certain sensory attributes as well as the potential impact of their preferences on self-reported willingness to adhere to prescribed allergic rhinitis therapy. We have reported, in a previous publication, the results of each attribute' s relative importance and patients' willingness to adhere to prescribed therapy. 8 Here, we quantify the strength of patient preference for INS sensory attributes in a monetary amount defined as the patients' willingness to pay using discrete choice experiment methodology, a form of conjoint analysis, which accommodates the integration of preference and cost. This information may inform both physician prescribing and formulary decision making. Because allergic rhinitis is a common disorder 13,14 that is associated with decreased quality of life 15 and lower worker productivity, 16 understanding strength of preferences may lead to a more informed selection of INS therapy, which, in turn, may improve patient satisfaction, adherence to therapy, and possibly lower economic burden.

Study Design and Participants
We conducted a two-part cross-sectional study of 120 patients with allergic rhinitis in 4 allergy and immunology clinics across the United States (n = 30 at each site in Georgia, Pennsylvania, Texas, and Utah) in November and December 2003. Participant inclusion/exclusion criteria are listed in Table 1. Investigators at the 4 allergy clinics were instructed to recruit patients through medical chart review or other relevant patient databases. The Essex Institutional Review Board (Lebanon, NJ) approved the study. This is the second part of a 2-part cross-sectional study of these 120 patients. In the first part of the study, the patients  8 In the second part of the study, reported here, discrete choice experiment methodology was used in which the patients chose among hypothetical INS products that differed in the intensity of the 6 sensory attributes and monthly copayments of $15, $30, and $50.

Discrete Choice Experiment Survey
Patients were administered an interactive computerized survey that elicited preferences using a discrete choice method, a form of conjoint analysis. [17][18][19][20] Conjoint analysis methods elicit preferences by showing respondents various hypothetical treatment options or health states that differ in terms of their core attributes and estimate strength of preference based on choice selection. We described the 6 sensory attributes in detail to patients: smell, taste, aftertaste, amount of spray running down throat (throat rundown), amount of spray running out of nose (nose runout), and feel of spray in nose/throat. These 6 sensory attributes were selected based on focus groups and cognitive debriefing studies that have shown them to comprehensively capture salient sensory perceptions of INSs. 10 Questionnaires using these attributes, such as the Sensory Perception Questionnaire, have shown good preliminary construct and content validity, and they have been used successfully in clinical trials of INSs. 9,10 By including different amounts of money as an attribute in a conjoint analysis study design, estimates of willingness to pay for changes in the levels of the attributes of importance can be derived. 21 Therefore, a seventh attribute, monthly copayment amount, was added to determine how much patients would trade-off sensory attributes for a monthly cost burden. In our study, all attributes were described in terms of 3 mutually exclusive intensity levels: mild, moderate, and severe ( Table 2). The levels described the varying quality of the attribute.
In the discrete choice section of the survey, participants were shown questions that consisted of 3 sets of hypothetical products. Each hypothetical product included 1 level from each attribute and a monthly copayment amount (see Table 3 for an example question). The participant was asked to choose between the hypothetical products by indicating which product profile was preferable and the strength of their preference. Because all possible combinations of attribute levels cannot feasibly be shown to each respondent, the computer program randomly generated 8 choice sets for each participant from a design matrix that was sampled to ensure an orthogonal and balanced study design. 22,23 Patients were reminded that each hypothetical product had the same efficacy and adverse event profile, information consistent with that stated in allergic rhinitis consensus guidelines and reviews. 1-6 (The site coordinators were instructed to tell each participant prior to the start of the survey: "Please assume that the products [intranasal steroid sprays] you are asked about all work the same and have the same side effects. The only differences between the products are the ones asked about in the survey.") Patients were also reminded to consider the long-term impact of costs when considering the monthly copayment amounts presented in each question.
The survey concluded with demographic (age, gender, income) and clinical questions that included frequency of INS use, number of prior INS medications used, and coexisting comorbidities.

Pilot Study
Before initiating the full study, a 5-patient pilot study was conducted to determine if the survey was easy to understand and feasible. Results of the pilot study indicated that patients were able to understand the survey and found it easy to complete. There was no evidence of respondent fatigue.

Logic Check
To determine whether respondents were logically considering each choice set, we showed them 2 identical fixed choice sets that contained hypothetical products containing all mild, all moderate, or all severe levels of each attribute. Logically, respondents would be expected to select the "superior" choice set, in this case, the set with all attributes set at their mildest level and the lowest copayment. Respondents who did not choose the hypothetical INS with all mild attributes and the lowest copayment amount were assumed to be making inconsistent choices and were excluded from the analysis.

Outcomes and Statistical Analyses
Study outcomes were marginal willingness to pay for moderate or severe intensity levels compared with mild intensity levels of each attribute, share of preference (frequency that products containing a particular level of an attribute were chosen over the number of times that level was shown), and the effect of income on product selection. Using multinomial logistic regres-sion, we estimated the marginal effect sizes of all levels and effect size per monthly dollar spent. Dividing the marginal effect size of a level with the marginal effect of a dollar change in copay (obtained in the univariate analyses), we estimated the marginal willingness to pay for each level of each attribute. Because income level can affect willingness to pay, we examined preferences for sensory attributes stratified by annual household income category. All statistical analyses were conducted using Sawtooth Software (Sequim, WA). Ninety-five percent confidence intervals that did not include 0 were considered to be statistically significant. If a level was statistically significant based on logistic regression, we rejected the null hypothesis that that level was equal to the lowest attribute level.

II Results
Of 120 patients who met the study criteria, approximately two thirds were women, the mean age was 39 years, and the majority were white (Table 4). A little fewer than half reported using INS products regularly (patients were required to choose either "regularly," "only sometimes," or "other"; the definition of these terms was left to each patient' s interpretation) and more than half had experience with 3 or more INS products. We excluded 7 patients from the analysis due to inconsistent responses to the aforementioned logic checks, leaving 113 patients for analysis. These patients provided responses to 904 choice sets and selected from 2,712 hypothetical INS products.
Previous publication of results from this study reported the patient preferences for the 6 attributes. 8 These results showed that the most important attribute in selecting a product was aftertaste (in 28% of patients), taste (in 19%), throat rundown (in 18%), nose runout (in 12%), smell (in 11%), and feel of spray (in 7%). Results from the current willingness-to-pay analysis depict the strength of preference for product attributes through monetary units. Based on the univariate analyses, the marginal effect sizes of copayment or cost was -0.06 utility score per dollar. For every $1 increase in price, there was a downward utility trend in preference. Table 5 shows the  marginal willingness to pay to avoid certain sensory attributes of INS products. Comparing the severest intensity level of each sensory attribute with the mildest, patients were willing to pay more per month for an INS with no smell instead of strong smell, no taste instead of strong taste, no aftertaste instead of strong aftertaste, no throat rundown instead of a lot of throat rundown, no nose runout instead of a lot of nose runout, and a wet feel instead of a dry feel. Comparing the moderate intensity levels of each sensory attribute with the mildest, only aftertaste, throat rundown, and nose runout had statistically significant monthly willingness to pay (Table 5). When examined independently, preferences usually declined with increasing intensity levels of sensory attributes and with the increased amount of copayment. However, when copayment was incorporated into the model by examining patients' selection of products by differing amounts of copayment, a different pattern emerged. In this case, product selections for mild and moderate levels of individual sensory attributes at almost any level of copayment were similar (Figures 1A-F), whereas product selection for severe levels of sensory attributes at the lower levels of copayment were markedly different.

Example of a Choice Set
Higher annual household income level did not change the share of preference for smell, taste, aftertaste, and feel of spray.
However, patients with a higher income were willing to pay more to avoid a lot of throat rundown and nose runout than those with a low income (Figures 2A-B; P <0.01). Subgroup willingness-to-pay analysis of other demographic groups (frequent vs. intermittent INS users, age groups, gender, comorbid conditions) did not appreciably differ from our main findings (data not shown).

II Discussion
Marginal willingness to pay depicts the strength of preference for product attributes through monetary units and has the advantage of providing easy-to-understand comparisons. Attribute levels with greater willingness to pay are more preferable than those with less willingness to pay. We found that patients with allergic rhinitis are willing to pay higher monthly copayments for products with mild intensity levels of each sensory attribute than those with higher intensity levels; that is, patients were willing to pay from $6 (spray with a wet feel) to $20 (for no aftertaste) to avoid the more severe intensity levels of a given attribute. Patients selected products with mild attribute intensity levels between 60% and 70% of the time when those products were presented. Aftertaste, throat rundown, and nose runout seemed to have higher willingness to pay to avoid both   moderate and severe intensity levels. Smell, taste, and feel of spray had higher willingness to pay to avoid only the severe intensity level. This information may inform prescribing and formulary decisions. Based on results reported by the authors previously, 8 individual preferences for INS sensory attributes had some variation, e.g., some patients placed strong emphasis on aftertaste only, while others rated aftertaste and smell as equally important.

Patients' Marginal Monthly Willingness to Pay* to Avoid Certain INS Sensory Attributes
Other investigators have shown that patients perceive differences in INS sensory attributes and have preferences for certain attributes. Meltzer et al. 24 conducted a double-blind, crossover study of 100 patients with symptomatic allergic rhinitis randomized to receive mometasone furoate nasal spray (MFNS) 200 mcg followed by fluticasone propionate nasal spray (FPNS) 200 mcg, or vice versa, after which they rated the drugs using a sensory attribute questionnaire. The investigators reported that fewer patients perceived scent, immediate taste, and aftertaste with MFNS compared with FPNS; in addition, more than half of the patients expressed a preference for MFNS and stated that they would be likely to comply with this treatment (i.e., use it daily as directed).
Kaliner conducted 2 telephone surveys-1 with 100 family practitioners, general practitioners, and internists 25 and 1 with 503 patients with seasonal and perennial allergic rhinitis 26 -and found that 95% of physicians thought that their patients would prefer an INS with no aftertaste and no smell. 25 However, the author noted that 47% to 60% of patients reported that their physicians had not asked them about their satisfaction with the sensory attributes of the INS they were using, 26 and only 7% of physicians mentioned that they chose an INS because of patient preferences. 25 In addition, 86% of patients reported that they had not complained to their physician about a sensory attribute of their INS treatment. 26 These study results suggest that improved physician-patient communication about sensory attributes could improve selection of INSs. However, a description of sensory attributes is not part of current product labeling.
In the present study, monthly copayment amounts reduce product attribute preference and attenuate the differences between intensity levels. However, even at the highest monthly copayment of $50, patients had a higher share of preference for product attributes with milder intensity levels, suggesting that sensory attributes are important in patient decision making. We also found that income level affects willingness to pay, but this was not a consistent finding. Patients with incomes >$80,000 per year were willing to pay more to avoid excess throat rundown than those with incomes <$40,000 per year.
Choosing INS products that better fit patients' INS sensory attribute preferences may increase adherence. 8 In his telephone survey of 503 patients with seasonal and perennial allergic rhinitis, Kaliner noted that 45% of patients stated that sensory attributes do influence how often they use INSs. 26

Limitations
Foremost among the limitations of this study is its small sample size, involving only 113 patients distributed among 4 states. The population was also largely white and middle class, which limits the ability to generalize the results without further replication in more diverse samples.
Second, we did not identify, analyze, or report whether the study patients had seasonal or perennial rhinitis, and severity of symptoms has been found to be much higher among patients with perennial allergic rhinitis who are more likely to take an oral antihistamine than are patients with seasonal allergic rhinitis. 26 Third, patients may not indicate consistent preferences if they have little experience with INS products. We sought to address this limitation by enrolling patients with allergic rhinitis www.amcp.org Vol. 12

B. Effect of Income Level on Nose Runout
No Running Some Running A Lot of Running L I N who had been diagnosed at least 1 year before and had used an INS within the last month. Our sample had been diagnosed with allergic rhinitis for a mean duration of 17.2 years with 86.7% of the patients having experience with 2 or more INS products.
Fourth, marginal willingness to pay may not necessarily predict real-life purchasing decisions.
Fifth, our analysis was limited to INS products and did not consider oral antihistamines and other therapeutic options in the treatment of allergic rhinitis.
Our study findings on patients' willingness to pay might be added to the information already available regarding barriers to informed patient decision making such as the lack of knowledge about treatment options, reluctance to discuss treatment with physicians, no inquiry by physicians about patients' preferences, or time constraints in physician schedules. 27,28 Routine patient-physician discussions could improve INS selection and should be encouraged.

II Conclusion
We found that patients are willing to pay significant higher monthly copayments to avoid certain sensory attributes of INSs. Given the high prevalence of allergic rhinitis, its adverse effects on quality of life, and sizable social and economic costs, methods to promote physician-patient dialogue about sensory attributes are advisable. Personal preferences may also be important in selecting INS agents for drug formulary placement in copayment tiers. Understanding the strength of patient preferences for INS sensory attributes may lead to more informed selection of pharmacotherapy for allergic rhinitis.